Linked Life Data

14973553

Source:http://linkedlifedata.com/resource/pubmed/id/14973553

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-2-19
pubmed:abstractText
Recently, we cloned a novel sulfatase domain-containing downregulated gene, HSulf-1, which modulates heparin-binding growth factor signaling in ovarian cancer. Based on the pilot data showing the loss of HSulf-1 in head and neck squamous cell carcinoma cell lines (SCCHN), we sought to employ SCCHN as a model to define the role of HSulf-1 in the molecular regulation of tumorigenicity. Three SCCHN lines (012SCC, WMMSCC, and 015SCC) had no detectable HSulf-1 mRNA. Clonal lines of HSulf-1-expressing 012SCC attenuated the activation of ERK/mitogen-activated protein kinase (MAPK) signaling mediated by fibroblast growth factor (FGF-2) and both ERK/MAPK and Akt signaling mediated by hepatocyte growth factor (HGF). Consistent with this downregulation, phosphorylation of HGF receptor, c-Met, which is frequently overexpressed in SCCHN, was also attenuated in HSulf-1 clonal 012SCC cell lines. HGF markedly enhanced the motility and migration of vector-transfected cells in a transwell invasion chamber. However, HGF-mediated motility and invasion was attenuated in HSulf-1 clonal 012SCC cell lines. In addition, transfected cells displayed significant growth inhibition concomitant with a decrease in mitogenicity, as measured by thymidine incorporation and increased sensitivity to staurosporine- and cisplatin-induced apoptosis. These data suggest that HSulf-1 normally functions as a negative regulator in cell growth and loss of HSulf-1 in SCCHN potentiates growth factor signaling, enhances motility, invasiveness and inhibits stress-induced apoptosis, with a resulting increase in tumorigenicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1439-47
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:14973553-Apoptosis, pubmed-meshheading:14973553-Carcinoma, Squamous Cell, pubmed-meshheading:14973553-Fibroblast Growth Factor 2, pubmed-meshheading:14973553-Head and Neck Neoplasms, pubmed-meshheading:14973553-Hepatocyte Growth Factor, pubmed-meshheading:14973553-Humans, pubmed-meshheading:14973553-Mitogen-Activated Protein Kinases, pubmed-meshheading:14973553-Neoplasm Invasiveness, pubmed-meshheading:14973553-Phosphatidylinositol 3-Kinases, pubmed-meshheading:14973553-Protein-Serine-Threonine Kinases, pubmed-meshheading:14973553-Proto-Oncogene Proteins, pubmed-meshheading:14973553-Proto-Oncogene Proteins c-akt, pubmed-meshheading:14973553-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:14973553-Signal Transduction, pubmed-meshheading:14973553-Sulfotransferases, pubmed-meshheading:14973553-Tumor Cells, Cultured
pubmed:year
2004
pubmed:articleTitle
HSulf-1 modulates HGF-mediated tumor cell invasion and signaling in head and neck squamous carcinoma.
pubmed:affiliation
Division of Gastroenterology and Hepatology, Mayo Clinic Cancer Center, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't